ABSTRACT
Background-Aim: While a frontal dysfunction is reported in post- SARS-CoV-2 with neurological symptoms (neuro-SARS-CoV-2), it is unclear whether this brain vulnerability is long lasting or reversible. The present study evaluated brain dysfunctions-as measured by FDG-PET-in neuro-SARS-CoV-2 over time to provide a better understanding of physiopathology underlying central nervous system involvement. Methods: 26 patients with neuro-SARS-CoV-2 were included. Seven patients were in the acute, the others in the sub-acute and chronic phase, namely, four at 1-month, four at 2-months, four at 3-months, four at 5 months and four at 7-9-months after onset. Patients underwent FDG-PET exams, clinical and cognitive evaluations. One patient was evaluated longitudinally, during the acute phase, and at a 5-months follow-up. Brain metabolism was analysed at the singlesubject and group levels by a comparisons with healthy controls. Correlations between severity/extent of hypometabolism and clinical variables of interest (global cognitive cognition, blood oxygen level saturation, and inflammatory status -C-reactive protein measurements) were also assessed. Results: Patients with acute neuro-SARS-CoV-2 showed the most severe and diffuse cortical hypometabolism, affecting almost all cortical areas. 2-months after the acute infection, a significant decrease in hypometabolism extension emerged, affecting mainly the frontal and temporal cortex. At 5-months after the acute phase, a recovery of cortical hypometabolism was evident, with limited residual clusters in frontal regions. At 7-9-months, no regions with brain hypometabolism were present. The only patient evaluated longitudinally showed a significant brain metabolic improvement from the acute phase (with diffuse cortical hypometabolism) to a 5-months follow-up (brain hypometabolism limited to frontal areas). Of note, the extent and severity of hypometabolism were associated with severe global cognitive dysfunctions, low blood oxygen level saturation, and high inflammatory status in all patients. Conclusions: These findings suggest that cortical functional impairment observed in patients with neuro-SARS-CoV-2 infection is likely to be transient and almost reversible, possibly due to synergistic effects of systemic virus-mediated inflammation sustained by systemic cytokine release and transient hypoxia inducing reversible neural dysfunction and local microglial activation.